Project description:Ergothioneine (ET), a dietary thione/thiol, is receiving growing attention for its possible benefits in healthy aging and metabolic resilience. Our study investigates ET's effects on healthspan in aged animals, revealing extension of lifespan and enhanced mobility in Caenorhabditis elegans, accompanied by improved stress resistance and reduced age-associated biomarkers. In aged rats, ET administration enhances exercise endurance, muscle mass, and vascularization, concomitant with higher NAD+ levels in muscle. Mechanistically, ET acts as an alternative substrate for cystathionine gamma lyase (CSE), stimulating H2S production, which increases protein persulfidation of more than 300 protein targets. Among these, protein persulfidation-driven activation of cytosolic glycerol-3-phosphate dehydrogenase (cGPDH) primarily contributes to the ET-induced NAD+ increase. ET’s effects are abolished in models lacking CSE and cGPDH, highlighting essential role of H2S signaling and protein persulfidation. These findings elucidate ET's multifaceted actions and provide insights into its therapeutic potential for combating age-related muscle decline and metabolic perturbations.
Project description:Ergothioneine (ET), a dietary thione/thiol, is receiving growing attention for its possible benefits in healthy aging and metabolic resilience. Our study investigates ET's effects on healthspan in aged animals, revealing extension of lifespan and enhanced mobility in Caenorhabditis elegans, accompanied by improved stress resistance and reduced age-associated biomarkers. In aged rats, ET administration enhances exercise endurance, muscle mass, and vascularization, concomitant with higher NAD+ levels in muscle. Mechanistically, ET acts as an alternative substrate for cystathionine gamma lyase (CSE), stimulating H2S production, which increases protein persulfidation of more than 300 protein targets. Among these, protein persulfidation-driven activation of cytosolic glycerol-3-phosphate dehydrogenase (cGPDH) primarily contributes to the ET-induced NAD+ increase. ET’s effects are abolished in models lacking CSE and cGPDH, highlighting essential role of H2S signaling and protein persulfidation. These findings elucidate ET's multifaceted actions and provide insights into its therapeutic potential for combating age-related muscle decline and metabolic perturbations. To better understand the role of ET the cells, we used thermal proteome profilling of cells treated or not with ergothionine, allowing us to find new targets for the compound including CSE.
Project description:The nematode Caenorhabditis elegans was treated with extracts of the Traditional Chinese Medicine plants Cuscuta chinensis and Eucommia ulmoides from the L4 stage. In aged worms (on the 7th and 12th day of adulthood) different health parameters were determined. Besides the prolongation of lifespan, we found that C. chinensis improved the swimming behavior, pharyngeal pumping rate, stress resistance, mechanosensation and memory of aged C. elegans. Furthermore, the extract treatment reduced the autofluorescence, which is a known biomarker of ageing. Thus, we concluded that C. chinensis is an overall healthspan enhancer. In contrast, the E. ulmoides extract specifically enhanced the lifespan and stress resistance of aged C. elegans, but did not improve any other health aspect. To reveal the mechanism behind the healthspan enhancing effects of C. chinensis, the transcriptome of treated and untreated C. elegans on the 12th day of adulthood was analysed. For comparison purposes, E. ulmoides treated nematodes were included in the analysis.
Project description:Caffeine is a globally consumed stimulant that has beneficial effects on biological processes including metabolism and aging, but its causal role in physiology remains incompletely understood. By using the roundworm Caenorhabditis elegans, here we show that caffeine extends lifespan by eliciting transcriptional remodeling that enhances lysosomal lipolysis. We found that transcriptomes of aged, caffeine-fed animals shifted toward youthful states. We also showed that caffeine induced a dietary restriction (DR)-like transcriptional program. Comparison with eat-2 mutants (a genetic DR model) identified commonly upregulated genes including the lysosomal lipases lipl-1 and lipl-2. The induction of lipl-1 and lipl-2 was required for increased lifespan and reduced neutral lipid accumulation by caffeine intake. Together, these findings indicate that caffeine promotes longevity in a DR-like metabolic reprogramming by enhancing lysosome-driven lipolysis.